The overall objective of the proposed research is to develop an experimental protocol for isolating and purifying defective Friend spleen focus forming virus (SFFV), and to investigate SFFV's potential as a suppressive agent, a defective interfering (DI) virus particle, and as a defective probe for the detection of other leukemia viruses (MuLV) of murine origin (i.e., ecotropic and perhaps xenotropic MuLVs). An attempt will be made to effectively isolate SFFV free of detectable MuLV helper utilizing the recent observation that SFFV differs significantly from MuLV helpers in its rate of sedimentation in linear (5-20%) sucrose density gradients. SFFV derived from sedimentation gradients will be further analyzed to determine its buoyant density (isopycnic banding in linear 25-50% sucrose gradients), and its oncogenic potential. Following the derivation of clonal isolates of SFFV from productively infected NIH Swiss mouse embryo fibroblasts (MEF), an in vitro microtestplate system will be used to determine if SFFV alone can immunosuppress T- and B-cell functions. Further, SFFV's ability to function as a DI particle and interfere with MuLV functions will be investigated. I shall also attempt to define the importance of SFFV structural antigens as targets for humoral immune surveillance mechanisms, and to determine if purified SFFV can be used as a sensitve probe for detecting viral helper functions specifically associated with infectious MuLVs.